Cannabinoids is a “No-Go” While a Cancer Patient is on Immunotherapy; but is It Safe to Use Psychedelics During Cancer Immunotherapy?

Introduction

Immunomodulation is a key mechanism by which cancers evade host immunity, and immune checkpoint inhibitors (ICIs) such as antibodies targeting PD-1/PD-L1 and CTLA-4 have become important antineoplastic therapies by releasing this inhibition to restore antitumour immune activity. At the same time, cannabinoids and classical psychedelics (serotonergic hallucinogens) are increasingly used by people with cancer for symptom relief, including anxiety, depression, pain, cachexia and inflammation. Earlier preclinical and some clinical work has raised concern that cannabinoids can diminish ICI efficacy, while in vitro studies have suggested that certain psychedelics may exert anti-cancer or anti-inflammatory effects through modulation of innate and adaptive immunity; however, evidence about how psychedelics affect tumour growth in vivo and whether they interact with ICIs during cancer therapy is lacking. Romach and colleagues set out to perform a small-scale preclinical evaluation of two psychedelic agents — lysergic acid diethylamide (LSD) and a psilocybin-containing mushroom extract — using in vitro cytotoxicity assays and an in vivo syngeneic mouse model of E0771 breast cancer, both alone and in combination with an anti-PD-1 antibody. The study aimed to test whether psychedelic exposure influences cancer cell viability and tumour growth, and whether such exposure might interfere with PD-1 inhibitor activity, given possible immunomodulatory effects mediated principally via the serotonin 5-HT2A receptor.